Chorionic villus biopsy, a technique for obtaining fetal cells for prenatal diagnosis, is now actively being investigated. Detection of genetic defects by amniocentesis has made significant contributions to medical genetics, but chorionic villus biopsy may offer access to prenatal diagnosis to a much larger group of women who do not find second trimester procedures acceptable. There will be a rapid increase in the utilization of chorionic villus biopsy and, therefore, a study of the safety and accuracy of this procedure is urgently needed. To accomplish this a collaborative effort of a number of centers utilizing the same protocol is required. A model protocol is presented for patient enrollment, genetic counseling, pregnancy dating, cervical culture, procedure performance, sample processing, data collection, and procedure assessment. This will allow establishment of (1) the accuracy of chorionic villus biopsy in identification of genetically abnormal embryos/fetuses, and (2) the rate of such complications as spontaneous abortions, low birth weight, prematurity placental abruption, Rh isoimmunization, fetal malformations, and neonatal developmental delay associated with chorionic villus sampling.